Open AccessBiphasic Regulation of Na + -HCO 3 − Cotransporter by Angiotensin II Type 1A Receptor
Author(s) -
Shoko Horita,
Yanan Zheng,
Chiaki Hara,
Hideomi Yamada,
Motoei Kunimi,
S. Taniguchi,
Shu Uwatoko,
Takeshi Sugaya,
Atsuo Goto,
Toshiro Fujita,
George Seki
Publication year - 2002
Publication title -
hypertension
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.986
H-Index - 265
eISSN - 1524-4563
pISSN - 0194-911X
DOI - 10.1161/01.hyp.0000036449.70110.de
Subject(s) - valsartan , angiotensin ii , medicine , endocrinology , chemistry , cotransporter , stimulation , angiotensin ii receptor type 1 , receptor , arachidonic acid , renin–angiotensin system , antagonist , biology , biochemistry , sodium , enzyme , organic chemistry , blood pressure
Although angiotensin (Ang) II is known to regulate renal proximal transport in a biphasic way, the receptor subtype(s) mediating these Ang II effects remained to be established. To clarify this issue, we compared the effects of Ang II in wild-type mice (WT) and Ang II type 1A receptor–deficient mice (AT1A KO). The Na+ -HCO3 − cotransporter (NBC) activity, analyzed in isolated nonperfused tubules with a fluorescent probe, was stimulated by 10−10 mol/L Ang II but was inhibited by 10−6 mol/L Ang II in WT. Although valsartan (AT1 antagonist) blocked both stimulation and inhibition by Ang II, PD 123,319 (AT2 antagonist) did not modify these effects of Ang II. In AT1A KO, in contrast, this biphasic regulation was lost, and only stimulation of NBC activity by 10−6 mol/L Ang II was observed. This stimulation was blocked by valsartan but not by PD 123,319. More than 10−8 mol/L Ang II induced a transient increase in cell Ca2+ concentrations in WT, which was again blocked by valsartan but not by PD 123,319. However, up to 10−5 mol/L Ang II did not increase cell Ca2+ concentrations in AT1A KO. Finally, the addition of arachidonic acid inhibited the NBC activity similarly in WT and AT1A KO, suggesting that the inhibitory pathway involving P-450 metabolites is preserved in AT1A KO. These results indicate that AT1A mediates the biphasic regulation of NBC. Although low-level expression of AT1B could be responsible for the stimulation by 10−6 mol/L Ang II in AT1A KO, no evidence was obtained for AT2 involvement.